rs32209

Variant names:

• chr5-128286799-T-A
• NM_001999.4:c.6931A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-128286799-T-A
• chr5-128286799-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001999.4(FBN2):​c.6931A>T​(p.Met2311Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,644 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M2311V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FBN2 NM_001999.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

Genes affected

FBN2 (HGNC:3604): (fibrillin 2) The protein encoded by this gene is a component of connective tissue microfibrils and may be involved in elastic fiber assembly. Mutations in this gene cause congenital contractural arachnodactyly. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FBN2	NM_001999.4	c.6931A>T	p.Met2311Leu	missense_variant	Exon 55 of 65	ENST00000262464.9	NP_001990.2
FBN2	XM_017009228.3	c.6778A>T	p.Met2260Leu	missense_variant	Exon 54 of 64		XP_016864717.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FBN2	ENST00000262464.9	c.6931A>T	p.Met2311Leu	missense_variant	Exon 55 of 65	1	NM_001999.4	ENSP00000262464.4
FBN2	ENST00000703783.1	n.3715A>T		non_coding_transcript_exon_variant	Exon 30 of 38

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461644 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.066
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.24	T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.092
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.72	T;.;.
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	-0.95	N;.;N
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.79	N;.;N
REVEL	Benign	0.24
Sift	Benign	0.51	T;.;T
Polyphen		0.0030	B;.;B
Vest4		0.23
MutPred		0.47		Loss of disorder (P = 0.0645);.;Loss of disorder (P = 0.0645);
MVP		0.37
MPC		0.22
ClinPred		0.76	D
GERP RS		5.3
Varity_R		0.12
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-127622491;